In this proposal we plan to use both in vivo and in vitro techniques to further our understanding of the physiological mechanism which regulates both serum and tissue gastrin concentration. In the experiments to be outlined below we will attempt to identify the dietary constituents which are responsible for the induction of the postprandial increase in gastrin rlease, as well as the luminal and possibly paracrine factors which play an important role in maintaining serum gastrin levels within physiological limits. Insight into the paracrine regulation of gastrin release will be obtained in our studies investigating the relationships between gastrin and somatostatin secretion from rodent antral mucosal explants maintained in organ culture. An isolated and enriched G cell preparation which has been developed in our laboratory will be used to rapidly screen putative gastrin secretory stimulants and inhibitors. We will also attempt to modify this cell separation technique to increase our final purity of G cells to 75% or better, so that the stimulus-secretion coupling mechanism of the G cell can be investigated. Another aspect of this proposal is an investigation of gastrin biosynthesis which may occur in two steps 1) biosynthesis of a gastrin precursor, 2) enzymatic conversion of this precursor to the active hormone. In the last series of experiments to be discussed in this proposal we will investigate how these cellular properties regulating gastrin secretion and formation are altered in diseased states resulting in hypergastrinemia.